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Crisis Response Journal Crisis Response Journal

Antibiotic resistant bacteria SNAPP to attention

Posted on 26th November 2016 at 17:09pm

The emergence and spread of antibiotic resistant pathogens has become a global crisis. Since the discovery of penicillin in 1928 by Alexander Fleming, and its subsequent integration into medical care, bacterial resistance is a known consequence to antibiotic overuse and abuse. A 2013 report by the Centers for Disease Control (CDC) estimates that around two million illnesses and 23,000 deaths each year in the US can be attributed to antimicrobial resistance. In Europe, 400,000 people present to hospitals with a resistant strain of bacteria and about 25,000 of them die each year according to the World Health Organization (WHO).

Three-dimensional illustration showing biofilm of antibiotic-resistant bacteria (Kateryna Kon/123rf)

The emergence and spread of multi-drug resistant organisms (MDRO) is slowly creating a world where people will die from simple infections such as a urinary tract infection. Last resort antibiotics like colistin are becoming obsolete in certain diseases and conditions, leaving medical professionals in a difficult place when it comes to providing care to their patients. Hospital-acquired infections, or nosocomial infections, are particularly worrisome as they affect the most vulnerable of patients –the old, young and immunocompromised – and are often highly resistant to common antibiotics.

Hospitals are breeding grounds for MDROs, making them key battlefields for fighting antibiotic resistance. They contain thousands of people, both staff and patients that each can facilitate the spread of pathogens through poor hand hygiene, unsecure ventilation, contaminated medical equipment and invasive procedures to name a few.

Antibiotic stewardship programmes are incredibly important in ensuring that patients are treated appropriately without the overuse or misuse of antibiotics. According to the Infectious Disease Society of America, these programmes are intended to co-ordinate interventions that improve and measure the use of antimicrobials. They promote selecting the right drug, dose, duration and route of administration. The ultimate goal of an antimicrobial stewardship is to facilitate use of the best possible antibiotic, reduce toxic side effects, decrease hospital costs due to infections and limit the extent of MDROs.

A recent study published in Nature Microbiology by Shu J Lam, a graduate student at the University of Melbourne, introduces Structurally Nanoengineered Antimicrobial Peptide Polymers (SNAPPs) as a promising defence against antibiotic resistant infections. Lam tested her SNAPPs on a total of six species of bacteria: two Gram-positive bacteria (Streptococcus mutans and Staphylococcus aureus) and four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii).

While her research is still in its beginning stages, its potential for combating resistance is promising. Her in vitro experiments showed relatively equal potency for all tested bacteria, killing both regular strains and colistin multidrug resistant (CMDR) strains at fairly equal doses. Other antimicrobial peptides are more specific to bacterial species in their effectiveness.

High doses, or a combination of antibiotics are the current treatments for resistant bacteria. However, side effects can be serious and the dissemination of antibiotic-resistant genes is more likely, thus making these treatments unfavourable. The minimum drug concentration of SNAPPs that resulted in quantitative cell death held relatively constant throughout the experiment; for example over 600 generations of both regular and CMDR A baumannii were killed at relatively equal doses of SNAPP. These results suggest that resistance to SNAPPs is not easily acquired. The researchers state that this is because SNAPPs work by disrupting the cell membrane of the bacteria through various mechanisms and trigger an apoptotic-like cell death. As for toxicity, when incubated with fresh red blood cells, less than 30 per cent of blood cells were affected, even at high concentrations.

Lam ran an in vivo experiment using mice infected with A baumannii. She injected the bacteria into the rats’ peritoneal space then compared the effectiveness of SNAPPs with powerful antibiotics – in this case imipenem – and a no treatment condition. When infected with wild-type A baumannii, the SNAPP-treated and imipenem-treated mice all survived. When infected with CMDR A baumannii however, the imipenem-treated and control group had comparably low rates of survival, while all of the SNAPP-treated mice survived. It appears that toxicity for the host is low and the SNAPPs are as effective as antibiotics with a much lower risk of conferring resistance.

Lam found the SNAPPs to be effective against bacteria that are often the source of hospital-acquired infections. According to the CDC, about one in 25 people has at least one hospital-acquired infection on any given day and around 75,000 have died of such an infection during their hospitalisation in the US, while in the European Union five to 12 per cent of patients acquire a nosocomial infection. Once an infection is acquired, antibiotic resistance can make treatment very complex. SNAPPs present an exciting alternative in these cases and could become a revolutionary treatment in the coming years with low toxicity and high effectiveness. However, Lam has said it is still too early for clinical trials.

To read CRJ's article by Dr Marc Mendelson (published September 2016) - click here

In the meantime, something like a pre-vaccination programme may be useful in managing resistance in hospital-acquired infections. A study of patients with autoimmune inflammatory disease found that pre-vaccination decreased infectious complications. Adherence to vaccination schedules for the general population is crucial for preventing diseases. A 2013 study on the effectiveness of the two-dose varicella vaccination found incidences of the disease to be decreased by 98 per cent since the initial introduction and roughly another 70 per cent after the introduction of the second dose. Immunisation of the general population should be closely monitored and highly encouraged.

Using pre-vaccination protocols could greatly reduce the number of antibiotics distributed for common hospital infections by reducing the need for them. There are already vaccination programmes in place in centres where acquiring an infection is likely, as in burn centres, where patients are given either antibodies or a vaccine for tetanus.

Patients going in for elective surgery, such as a splenectomy, are usually vaccinated against several infections a few weeks prior to their surgery in order to give their immune system a boost post-surgery. Such programmes could be expanded into other elective surgeries and long-term stays involving invasive procedures in order to prevent infections.

Even if microbial resistance prevention fails, SNAPPs could be a safe and effective alternative treatment for antibiotic resistant infections.

By Silvi Dore, Anna Roselle, Carly Esteves and Ian Portelli

References:

  • Antibiotic / Antimicrobial Resistance. (2016, August 17). Centers for Disease Control and Prevention. Retrieved November 02, 2016.
  • Antibiotic Resistance Threats in the United States, 2013. (2014). Centers for Disease Control and Prevention. Retrieved November 2, 2016.
  • Bialek, S et al (2013). Impact of a Routine Two-Dose Varicella Vaccination Program on Varicella Epidemiology. Pediatrics, 132(5), 1-7. doi:10.1542/peds.2013-0863
  • Fernandez-Martinez, S. et al. (2016). Effectiveness of a systematic vaccination program in patients with autoimmune inflammatory disease treated with anti-TNF alpha drugs.
  • Expert Opinion on Biological Therapy, 16(11), 1317-1322. DOI: 10.1080/14712598.2016.1218844, Fleming, Alexander. (1945, December 11). Penicillin. Nobel Prize.
  • Healthcare-associated Infections. (2016, March 2). Centers for Disease Control and Prevention. Retrieved November 02, 2016.
  • Lam, S J  et al. (2016). Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers. Nature Microbiology, 1, 1-11. DOI: 10.1038/NMICROBIOL.2016.162.
  • Mehta, Y et al. (2014). Guidelines for prevention of hospital acquired infections. Indian J Crit Care Med, 18(3), 149-163. doi: 10.4103/0972-5229.128705.
  • Vaccines That Might Be Indicated For Adults Aged 19 Years or Older Based On Medical and Other Indications. (2016, February 1). Centers for Disease Control and Prevention. Retrieved November 02, 2016.

 

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